The Interaction of Selective A1 and A2A Adenosine Receptor Antagonists with Magnesium and Zinc Ions in Mice: Behavioural, Biochemical and Molecular Studies.

Affiliation

Szopa A(1), Bogatko K(1), Herbet M(2), Serefko A(1), Ostrowska M(2), Wośko S(1), Świąder K(3), Szewczyk B(4), Wlaź A(5), Skałecki P(6), Wróbel A(7), Mandziuk S(8), Pochodyła A(3), Kudela A(2), Dudka J(2), Radziwoń-Zaleska M(9), Wlaź P(10), Poleszak E(1).
Author information:
(1)Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, 1 Chodźki Street, PL 20-093 Lublin, Poland.
(2)Chair and Department of Toxicology, Medical University of Lublin, 8 Chodźki Street, PL 20-093 Lublin, Poland.
(3)Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chodźki Street, PL 20-093 Lublin, Poland.
(4)Department of Neurobiology, Polish Academy of Sciences, Maj Institute of Pharmacology, 12 Smętna Street, PL 31-343 Kraków, Poland.
(5)Department of Pathophysiology, Medical University of Lublin, 8 Jaczewskiego Street, PL 20-090 Lublin, Poland.
(6)Department of Commodity Science and Processing of Raw Animal Materials, University of Life Sciences, 13 Akademicka Street, PL 20-950 Lublin, Poland.
(7)Second Department of Gynecology, 8 Jaczewskiego Street, PL 20-090 Lublin, Poland.
(8)Department of Pneumology, Oncology and Allergology, Medical University of Lublin, 8 Jaczewskiego Street, PL 20-090 Lublin, Poland.
(9)Department of Psychiatry, Medical University of Warsaw, 27 Nowowiejska Street, PL 00-665 Warsaw, Poland.
(10)Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033 Lublin, Poland.

Abstract

The purpose of the study was to investigate whether the co-administration of Mg2+ and Zn2+ with selective A1 and A2A receptor antagonists might be an interesting antidepressant strategy. Forced swim, tail suspension, and spontaneous locomotor motility tests in mice were performed. Further, biochemical and molecular studies were conducted. The obtained results indicate the interaction of DPCPX and istradefylline with Mg2+ and Zn2+ manifested in an antidepressant-like effect. The reduction of the BDNF serum level after co-administration of DPCPX and istradefylline with Mg2+ and Zn2+ was noted. Additionally, Mg2+ or Zn2+, both alone and in combination with DPCPX or istradefylline, causes changes in Adora1 expression, DPCPX or istradefylline co-administered with Zn2+ increases Slc6a15 expression as compared to a single-drug treatment, co-administration of tested agents does not have a more favourable effect on Comt expression. Moreover, the changes obtained in Ogg1, MsrA, Nrf2 expression show that DPCPX-Mg2+, DPCPX-Zn2+, istradefylline-Mg2+ and istradefylline-Zn2+ co-treatment may have greater antioxidant capacity benefits than administration of DPCPX and istradefylline alone. It seems plausible that a combination of selective A1 as well as an A2A receptor antagonist and magnesium or zinc may be a new antidepressant therapeutic strategy.